Esters of 2, 3-epoxypropylmalonic acid and their preparation



Patented Mar. 8, 1949 UNITED STATES PATENT OFFICE ESTERS OF2,3-EPOXYPROPYLMALONIC ACID AND THEIR PREPARATION Harold Levy and RalphDaniels, New York, N. Y., assignors, by mesne assignments, to William R.Warner & 00., Inc., New York, N. Y., a corporation of Delaware NoDrawing. Application February 25, 1946, Serial No. 650,125

2 Claims. (Cl. 260-348) wherein R may be an aliphatic or aromaticradical, such as Cal-I1, CeHs, etc. and R1 may be H or aliphatic. I

The esters of this invention may be prepared by reacting a compoundhaving the structural formula:

R1 onFonJm-omooom, wherein R and R1 have the same meanings ,as above,with peracetic acid, or with other peracids, such as perbenzoic acid andperphthalic acid.

This invention is further explained by the following examples which areintended for purposes of illustration and are not intended to beconstrued as limitations. v

EXAMPLE I Preparation of diethyl allylmalonate A solution of sodiumdiethyl malonate was .prepared in the usual manner from 34.5 grams (1.50atoms) of sodium, 750 ml. of absolute ethanol, and 241 grams (1.51moles) of diethyl malonate. To this solution was added allyl chloride(125.0 grams, 1.65 moles) during hour, with stirring and with noexternal heating or cooling. The reaction mixture was then refluxed 2hours.

The mixture was concentrated in vacuo at about 15 mm., using a bath atabout 55-60 0., to remove most of the alcohol. The residue was cooled toroom temperature and poured into 300 grams of an ice-water mixture. Tothis was added cold, sulfuric acid until a definite acid reaction wasachieved. The mixture was extracted with 7x100 ml. of ether and theether extract washed successively with 100 ml. of cold, saturated sodiumbicarbonate solution and 2X 100 ml. of cold water. The washed ethersolution was dried over anhydrous sodium sulfate, filtered, concentratedto remove ether, and the residue distilled. Two successive distillationsthrough a Widmer column, containing a 250 mm. spiral, and Fenske-typecolumn (625 mm. long, 10.5 mm. i. d., packed with 3 mm. glass helices,and arranged for total reflux and partial take-off) led to 164.6 grams(55% yield) of the diethyl allylmalonate,

. 2 boiling point 117-118 C. at 20 mm., 12,, 1.4278- 1.4281.

ExAurLr II Preparation of diethyl-(2,3-epozyprom l) malornate during 1%hours at 3035 C. The reaction mix-.

ture was then stirred for 2 hours and finally allowed to stand 20 hours,both at room tempera ture. The apparatus was protected from introductionof atmospheric moisture by placing tubes filled with anhydrous CaCl2 atall openings to the air.

The solution was analyzed for peracetic acid content by adding acidifiedpotassium iodide solution to an aliquot and then titrating the liberatediodine with standard thiosulfate solution. It was found to contain0.00154 moles per ml.

15 grams (0.075 moles) of the diethyl allylmalonate were added to amixture of 52 ml. of-the above solution containing 0.080 mole ofperacetic acid, 8 ml. of additional glacial acetic acid and 0.1 gram offused sodium acetate at 30 C. The reactants were protected fromatmospheric moisture by placing tubes filled with, e. g., anhydrous(39.01:, at all openings to the air. The solution was then maintainedfor 112 hours at room temperature (about 25 0.). It was thenconcentrated in vacuo (about 15 mm. of mercury pressure), using a bathat about 40-50 C. in order to remove most of the acetic acid. Theresidue was dissolved in ether ml.) and the solution washed successivelywith 25 ml. of 8% sodium bisulfite solution,.twice with saturated sodiumbicarbonate solution (25 ml. being used each time), and twice with water(25 ml. being used each time). The washed solution was dried overanhydrous sodium sulfate, concentrated to remove ether, and the residuewas distilled in vacuo (0.01-0.13 mm. of mercury pressure) up to a.temperature of about 149 C. A redistillation of 3.1 grams of thedistillate led to a yield of 2.4 grams of colorless liquid, boilingpoint 83-8'I C. under a pressure of 0.08 mm. of mercury, n =1.4362,

d4= =1.094'7, M =51.68, saponification equivalent=110. This was thedesired material, diethyl 2,3 epoxypropyl malonate having the structuralformula:

cn 7cn-cnr-cmcoo 0,11,

It was observed to have C, 55.62% and H, 7.27%. A second run involvedthe addition of the diethyl allylmalonate to the peracetic acidsolution, in 200% excess, at 50 C. and the maintenance of the resultingsolution at 50 C. for 6 hours and then at room temperature for 17 hours.The oxide was obtained in 32% yield. By using monoperphthalic acidinstead of peracetic acid and proceeding as above, an improved yield ofdiethyl- (2,3-epoxypropyl) -malonate was obtained.

EXAMPLE III Preparation of diethyl-(l-methyl-Z-propenyl)- malonate 20-28C. during the addition performed by pumping the sodium diethyl malonatefrom the vessel in which it was prepared into the reaction vessel undernitrogen gas pressure. The mixture was stirred for 45 minutes andallowed to stand at room temperature (about C.) over night (16-17hours). All of the foregoing operations were performed in the absence ofatmospheric moisture, this condition being attained by means of tubesfilled with, e. g., anhydrous CaClz. at all openings to the atmosphere.

The mixture was concentrated in vacuo (about 15 mm. mercury) to removemost of the ethanol by heating in a bath at -50 C. The residue wascooled to room temperature (circa 20 C.) and 100 ml. of ice and waterand then 10% sulfuric acid, bringing the pH to 6, were added. Theacidified solution was extracted three times with ether (75 ml. of etherbeing used each time) and the combined ether extracts were washedsuccessively with water (35 ml.), saturated sodium bicarbonate (50 ml.)and water (2X25 ml.).

The washed extract was dried over anhydrous sodium sulfate, filtered,concentrated to remove ether, and the residue was distilled.

The desired ester was obtained (10.2 grams) as a colorless liquid,boiling point 54 C. under 0.4 mm. mercury pressure to 56 C. under 0.25

mm. mercury pressure, n =l.4305-1.4311. Re-

distillation gave the pure compound, boiling point 61-62 C. under 0.3mm. mercury pressure, n =1.4310, d4 =0.9894, M =56.06.

EXAMPLE IV grams, 0.075 mole), prepared as described above, was mixedwith 252 ml. of an ether solution of monoperphthalic acid (0.150 mole,100%excess).

4 The mixture was kept 8 days in the dark at room temperature.

After 1 gram of fused anhydrous sodium ace tate was added the mixturewas stirred 1 hour each at room temperature and at reflux. About of theether was removed by distillation at atmospheric pressure and theconcentrated residue kept at room temperature for 45-hours.

The ether solution was filtered from precipitated phthalic acid, andthen washed successive- 1y with saturated sodium bisulfite (10 m1.),saturated sodium bicarbonate (5X15 ml.) and saturated sodium chloride(2X5 ml.). The ether solution was then dried over anhydrous sodiumsulfate, concentrated, and the residue distilled.

The epoxide was obtained in 51% yield (8.75 grams) as a colorlessliquid, boiling point 84 C. (0.11 mm. of. mercury)87 C. (0.20 mm.). n1.4387-1.4396.

The novel esters herein, prepared in accordance with the proceduredescribed above, are useful as intermediates in the preparation ofnumerous organic compounds. For example, they may be used in thepreparation ofbarbiturates. Many of the novel compounds are useful inthe preparation of biologically-active substances. In addition, thenovel compounds herein, being high boiling, viscous liquids, lendthemselves to use as plasticizers.

The foregoing illustrates the practice of this invention, which however,is not to be limited thereby but is to be construed as broadly aspermissible in view of the prior art and limited solely by the appendedclaims.

We claim:

1. Compounds having the structural formula wherein R is a memberselected from the group REFERENCES CITED The following references are ofrecord in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,974,917 Halbig Sept. 25, .19342,091,241 Kvalnes Aug. 24, 1937 2,237,265 Shoule Apr. 1, 1941 2,330,033DAlelio Sept. 21, 1943 OTHER REFERENCES 1 Gilman-Organic Chemistry. Vol.1, page 634.

Hackhs Chemical Dictionary by Grant, 3rd Edition, 1944, page 36.

